Over the past year, using the collagenase digestion technique, we have isolated islets from over 30 fresh human cadaver pancreata and have achieved a 3 to 100 fold purification of islets as reflected by the ratio of insulin to amylase in the isolated tissue; yield has varied from less than 1 to 50% of the total pancreata islet mass, but is usually low. Isolated human islets can synthesize insulin, proinsulin, and glucagon and can release insulin to respond to in vitro glucose stimulation. In experimental animals, survival has been prolonged in pancreatectomized pigs transplanted with isolated islets. In diabetic rats, intraperitoneal transplantation of isologous islet tissue has completely ameliorated the metabolic abnormalities, and has also reversed or halted progression of secondary diabetic renal lesions. For the coming year methods to improve the yield of islets from human cadaver pancreata will be developed. In vitro studies on isolated human islets will concentrate on defining a larger molecular weight intermediate of glucagon biosynthesis. In both human and experimental animals, agents to selectively inactivate or destroy pancreatic exocrine tissue will be used in conjunction with islet liberation by collagenase digestion; the islet tissue obtained will be transplanted to diabetic rats and dogs. Cryopreservation of rat islet tissue will be attempted. Methods of modifying islet allograft rejection either by treatment of the transplanted tissue or by treatment of the recipient rats will be evaluated.